betadex and Chemical-and-Drug-Induced-Liver-Injury

This study aimed to assess hepatotoxicity and nephrotoxicity of Lambda-cyhalothrin (LCT) and the protective effect of rutin alone and in combination with β-cyclodextrin (β-CD).. Male Wistar rats were divided into five groups: Group 1: was used as a control and received a standard diet and water. Group 2, 3, 4 and 5 were orally administered with LCT (7.6 mg/kg body weight), rutin (200 mg/kg body weight) LCT and rutin (at the same doses as in Group 2 and Group 3), and LCT and a mixture of rutin with β-CD (400 mg/kg body weight), respectively. All experimental animals were orally gavaged 5 days/week for 60 days.. Our data revealed that LCT-induced liver and kidney injuries were related to the up-regulated expression of TNF-α and down-regulated expression of NRF-2 genes mRNA, whereas these effects were reversed with rutin treatment. LCT-induced oxidative stress altered the histological picture, and the hematological and biochemical parameters.. Treatment with a rutin-β-CD complex had preventive potential against LCT via suppression of oxidative stress and augmentation of the antioxidant defense system.

Topics: Animals; Antioxidants; beta-Cyclodextrins; Body Weight; Chemical and Drug Induced Liver Injury; Male; Oxidative Stress; Rats; Rats, Wistar; RNA, Messenger; Rutin; Tumor Necrosis Factor-alpha

The excessive consumption of alcohol and the installation of dependence is, in most cases, facilitated by favorable psychological factors that trigger and maintain the behavior of consumers. Examples more frequently encountered in individuals having difficulty with alcohol are, in particular: one or more anxiety disorders, deficits in the capacities to manage stress and anxiety. The main objective of this work was to study in vivo the anti-addiction effect and hepatotoxicity of tow baclofen analogues complexed with β-Cyclodextrin (βCD) on an alcohol-dependent rat model.. The synthesis of two analogues, ABF1 and ABF2, close to baclofen was reported. The structural determination of the two compounds was confirmed by NMR and IR analysis. The complexation of analogues with β-Cyclodextrin (βCD) was performed in water at room temperature (25 °C). The interactions of ABF with β-Cyclodextrin, and the stability constant (Ka) of the inclusion complex formed between them were investigated by using UV-visible spectroscopy. The biological effects of baclofen and the two analogues on alcohol dependence were studied in wistar rats. The anti-addiction effect of the analogues was tested by measuring the alcohol intake and the variation of the animal behaviour. The toxicity of the compounds was also analysed on liver injury markers.. The amino-3-phenylbutanoic acid (ABF1) and 3,4,5-trihydroxy-N-(methyl-2-acetate) benzamide (ABF2) were synthesized. The complexation of both analogues of baclofen (BF) with β-cyclodextrin (βCD) (ABF- βCD) was realized and confirmed by the stability constant of the inclusion complex (Ka) and Job's method. The evaluation of anti-addiction activity in vivo showed that ABF1-βCD inhibits the consumption of alcohol at doses equivalent to those of baclofen. Both baclofen analogues have shown an anxiolytic effect. Regarding the toxicity of the two compounds, our results showed that ABF1-βCD has less toxic effect than baclofen; it reduces the activity of ALT and AST enzymes. Histologically, ABF1-βCD has no effect on the liver structure and has a protective effect against lesions alcohol-induced liver disease.. Therefore, it can be suggested that ABF1 analogue combined with β-Cyclodextrin can be used as a treatment for alcohol dependence. Further clinical works are needed to confirm its effectiveness.

Topics: Animals; Baclofen; beta-Cyclodextrins; Chemical and Drug Induced Liver Injury; Magnetic Resonance Spectroscopy; Rats

The nano-encapsulation of Periploca angustifolia phenolic extract using the macrocyclic carbohydrate polymers (β‑cyclodextrins) is a most approach compared with other encapsulation methods. In this work, the β‑Cyclodextrins-PAE complex stability has been evaluated by advanced analytical methods and techniques including HPLC, FTIR and XRD. The results showed that CdCl

Topics: Antioxidants; beta-Cyclodextrins; Cadmium; Catalase; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Glutathione; Glutathione Peroxidase; Hep G2 Cells; Humans; Lipid Peroxidation; Liver; Macrocyclic Compounds; Nanoparticles; Oxidative Stress; Periploca; Plant Extracts; Polymers; Protective Agents; Superoxide Dismutase

San Huang Shel Shin Tang (SHSST) is a traditional herbal decoction used as a hepato-protective agent and is composed of Rheum officinale Baill, Scutellaria baicalnsis Geprgi and Coptis chinensis Franch (2:1:1 w/w). Beta-cyclodextrin (β-CD) modification may potentially increase the solubility and spectral properties of SHSST.. In this research, the hepato-protective effects of unmodified SHSST, β-CD modified SHSST complex (SHSSTc) and silymarin were evaluated in carbon tetrachloride (CCl4) induced acute hepatotoxicity in rats.. SHHSTc (40 mg/kg/day) and silymarin (100 mg/kg/day) both decreased the CCl4-induced cirrhosis pathway-related transforming growth factor beta (TGF-β) and apoptosis pathway-related caspase-8 protein expressions, but SHSST (40 mg/kg/day) did not reduce TGF-β and caspase-8 significantly . Moreover, SHHSTc (40 mg/kg/day) enhanced the activation of insulin-like growth factor 1 receptor (IGF1R) mediated survival pathway than the silymarin (100 mg/kg/day) to protect the liver from damage induced by CCl4.. β-CD modification promotes hepato-protective effects of SHSST and reduces the required-dosage of the SHSST.

Topics: Animals; beta-Cyclodextrins; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Drug Synergism; Drugs, Chinese Herbal; Plant Extracts; Protective Agents; Rats

Stable hydrophilic C60(OH)10 nanoparticles were prepared from 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and applied to the treatment of an acetaminophen overdose induced liver Injury. C60(OH)10 nanoparticles were produced by cogrinding α-CD, β-CD, γ-CD and HP-β-CD and characterized in terms of solubility, mean particle diameter, ζ-potential and long term dispersibility in water. Hydrophilic C60(OH)10 nanoparticles with particle sizes less than 50 nm were effectively produced by cogrinding HP-β-CD with C60(OH)10 at a molar ratio of 1:3 (C60(OH)10:CD). The resulting C60(OH)10/HP-β-CD nanoparticles were stable in water and showed no aggregation over a 1 month period. The C60(OH)10/CDs nanoparticles scavenged not only free radicals (DPPH and ABTS radicals) but also reactive oxygen species (O2(•-) and •OH). When C60(OH)10/HP-β-CD nanoparticles were intraperitoneally administered to mice with a liver injury induced by an overdose of acetaminophen (APAP), the ALT and AST levels were markedly reduced to almost the same level as that for normal mice. Furthermore, the administration of the nanoparticles prolonged the survival rate of liver injured mice, while all of the mice that were treated with APAP died within 40 h. To reveal the mechanism responsible for liver protection by C60(OH)10 nanoparticles, GSH level, CYP2E1 expression and peroxynitrite formation in the liver were assessed. C60(OH)10/HP-β-CD nanoparticles had no effect on CYP2E1 expression and GSH depletion, but suppressed the generation of peroxynitrite in the liver. The findings indicate that the protective effect of C60(OH)10/HP-β-CD nanoparticles was due to the suppression of oxidative stress in mitochondria, as the result of scavenging ROS such as O2(•-), NO and peroxynitrite, which act as critical mediators in the liver injuries.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acetaminophen; Animals; Antioxidants; Benzothiazoles; beta-Cyclodextrins; Biphenyl Compounds; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP2E1; Drug Overdose; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Fullerenes; Glutathione; Hydrophobic and Hydrophilic Interactions; Hydroxylation; Liver; Male; Mice, Inbred C57BL; Nanoparticles; Nitric Oxide; Oxidative Stress; Particle Size; Peroxynitrous Acid; Picrates; Protective Agents; Solubility; Static Electricity; Sulfonic Acids; Tyrosine

The present study evaluated the antioxidant and hepatoprotective effects of the flavonoid naringenin (NGN) and its β-cyclodextrin formulation at a dose of 50 mg/kg b.w. The assessment was done by the investigation of serum-enzymatic and liver antioxidant activity, histopathological and ultrastructural changes in male Swiss mice, which were subjected to acute experimental intoxication with CCl4. Formulated and free flavonoid were orally given to mice for 7 days and then were intraperitoneally injected with 1.0 mL/kg CCl4 on the 8th day. After 24 h of CCl4 administration, an increase in the levels of transaminases aspartate aminotransferase and alanine aminotransferase activities and malondialdehyde concentration occurred and a significant decrease in superoxide dismutase, catalase glutathione-peroxidase activities, and glutathione levels was detected as well. These were accompanied by extended centrilobular necrosis, steatosis, fibrosis, and an altered ultrastructure of hepatocytes. Pretreatment with formulated or free flavonoid retained the biochemical markers to control values. Histopathological and electron-microscopic examination confirmed the biochemical results. In conclusion, both NGN and NGN/β-cyclodextrin complex showed antioxidant and hepatoprotective effects against injuries induced by CCl4.

Topics: Animals; Antioxidants; beta-Cyclodextrins; Cacao; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Citrus; Drug Delivery Systems; Flavanones; Lipid Peroxidation; Liver; Male; Phytotherapy; Plant Extracts; Rats, Wistar; Solanum lycopersicum; Superoxide Dismutase

Clotrimazole, a poorly water-soluble antimycotic agent, is a promising therapeutic agent for various diseases including cancer and sickle cell anemia. The oral bioavailability and hepatic toxicity of clotrimazole were compared with its beta-cyclodextrin inclusion form which was prepared by the spray-drying method. The inclusion complex gave significantly higher initial plasma concentrations, Cmax and AUC than did clotrimazole alone, indicating that the drug from the inclusion compound could be more easily absorbed in rats. Furthermore, mice treated with the inclusion compound showed significantly higher GOT/GPT values compared to clotrimazole alone. The inclusion compound also induced hypertrophy of hepatic cells by fat accumulation and disappearance of hepatic sinusoids, indications of pathological changes of liver, suggesting that the inclusion compound could induce more severe tissue damage in the liver than clotrimazole alone. Thus, hepatotoxicity of clotrimazole seems to be correlated with the enhanced oral bioavailability by inclusion complexation. Our results suggest that, in the development of a novel oral product, appearance or enhancement of hepatic toxicity must be considered along with oral bioavailability.

Topics: Alanine Transaminase; Animals; Antifungal Agents; Area Under Curve; Aspartate Aminotransferases; beta-Cyclodextrins; Chemical and Drug Induced Liver Injury; Chemistry, Pharmaceutical; Clotrimazole; Drug Carriers; Half-Life; Liver; Liver Function Tests; Male; Mice; Mice, Inbred ICR; Powders; Rats; Rats, Sprague-Dawley; Solubility

A 13-week oral toxicity study of beta-cyclodextrin was carried out in F344 rats at the dose levels of 10, 5, 2.5, 1.25, 0.6 and 0% in powdered diet. Each group consisted of 10 males and 10 females. All animals survived at the end of the experiment, while a slight decrease in body-weight gain was observed in males of the 10%- and 5%-groups. Dose-dependent increases in serum levels of GOT, GPT and alkaline phosphatase were observed in treated animals of both sexes, and increases in serum levels of urea nitrogen and relative liver weights in treated males. Histopathologically, a dose-dependent increase in the severity of inflammatory cell infiltration was seen in the liver of treated animals, focal hepatocellular necrosis being detected in both sexes of the 10%-group and females of the 5%-group. These findings indicate that beta-cyclodextrin causes hepatocellular injury to rats when it is orally administered.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; beta-Cyclodextrins; Chemical and Drug Induced Liver Injury; Cyclodextrins; Dose-Response Relationship, Drug; Female; Food Additives; Liver; Male; Organ Size; Rats; Rats, Inbred F344; Time Factors